In an effort to understand the origin of blood-pressure lowering effects observed in recent clinical trials with 11¦Â-HSD1 inhibitors, we examined a set of 11¦Â-HSD1 inhibitors in a series of relevant in vitro and in vivo assays. Select 11¦Â-HSD1 inhibitors reduced blood pressure in our preclinical models but most or all of the blood pressure lowering may be mediated by a 11¦Â-HSD1 independent pathway.